Anastrozole Jenepharm film-coated tablets 1 mg blister No. 28

Instructions Anastrozole Jenepharm film-coated tablets 1 mg blister No. 28

Composition

active ingredient: anastrozole;

1 tablet contains 1.0 mg of anastrozole;

excipients: lactose monohydrate, microcrystalline cellulose, sodium starch glycolate (type A), magnesium stearate, colloidal anhydrous silica, hydroxypropylcellulose, Opadry II White (lactose monohydrate, hypromellose, titanium dioxide (E 171), polyethylene glycol).

Dosage form

Film-coated tablets.

Main physicochemical properties: white, round, biconvex, film-coated tablets, without a score line, embossed with A1 on one side.

Pharmacotherapeutic group

Enzyme inhibitors.

ATX code L02B G03.

Pharmacological properties

Pharmacodynamics

Anastrozole is a potent and highly selective nonsteroidal aromatase inhibitor. In postmenopausal women, estradiol is mainly produced by the conversion of androstenedione to estrone in peripheral tissues by the enzyme aromatase. Estrone is further converted to estradiol. A decrease in circulating estradiol levels has a therapeutic effect in women with breast cancer. In postmenopausal women, taking anastrozole at a daily dose of 1 mg leads to an 80% decrease in estradiol levels. Anastrozole has no progestogenic or androgenic activity. Anastrozole at daily doses of up to 10 mg has no effect on cortisol and aldosterone secretion measured before and after a standard adrenocorticotropic hormone (ACTH) stimulation test. Therefore, replacement corticosteroids are not required.

Pharmacokinetics

Absorption of anastrozole is rapid, with peak plasma concentrations occurring within 2 hours (fasting). Anastrozole is eliminated slowly. The plasma half-life is 40-50 hours. Food slightly slows down the rate of absorption, but not its extent. Minor changes in the rate of absorption do not have a clinically significant effect on steady-state plasma concentrations when anastrozole is administered once daily.

Approximately 90-95% of steady-state concentrations are achieved after 7 days of dosing. There is no information on the time or dose-dependent pharmacokinetic parameters of anastrozole.

The pharmacokinetics of anastrozole are independent of age in postmenopausal women.

The pharmacokinetics of anastrozole in children have not been studied.

Only 40% of anastrozole binds to plasma proteins.

Anastrozole is extensively metabolized in postmenopausal women, with less than 10% of the dose excreted unchanged in the urine within 72 hours of dosing. Anastrozole is metabolized by N-dealkylation, hydroxylation, and glucuronidation. The metabolites are excreted primarily in the urine. The triazole, the major metabolite in plasma, does not inhibit aromatase.

The clearance of anastrozole in volunteers with stable cirrhosis or renal impairment did not differ from that in healthy volunteers.

Indication

Treatment of advanced hormone receptor-positive breast cancer in postmenopausal women.

Adjuvant treatment of early-stage invasive breast cancer with positive hormone receptors in postmenopausal patients.

Adjuvant treatment of early hormone receptor-positive invasive breast cancer in postmenopausal patients who have received 2-3 years of adjuvant tamoxifen therapy.

Contraindication

Anastrozole SANDOZ is contraindicated in patients:

• during pregnancy and breastfeeding;
• with known hypersensitivity to anastrozole or to any of the other components of the drug.

Interaction with other medicinal products and other types of interactions

Anastrozole inhibits cytochrome P450 1A2, 2C8/9 and 3A4 in vitro. Clinical studies with antipyrine and warfarin showed that anastrozole at a dose of 1 mg did not significantly inhibit the metabolism of antipyrine and R- and S-warfarin, indicating that concomitant use of anastrozole with other drugs is unlikely to result in clinically significant drug interactions mediated by CYP enzymes.

The enzymes mediating the metabolism of anastrozole have not been identified. Cimetidine, a weak non-specific inhibitor of CYP enzymes, did not affect the plasma concentrations of anastrozole. The effect of potent CYP inhibitors is unknown. The clinical significance of these findings remains unknown. Until further data are available, caution should be exercised when combining drugs that are metabolized by these enzymes. This is especially true for drugs with a narrow therapeutic index.

A review of the safety database accumulated during clinical trials did not reveal any clinically significant drug interactions in patients taking anastrozole concomitantly with other commonly prescribed drugs.

Tamoxifen or estrogen-containing agents should not be administered concomitantly with Anastrozole Sandoz as this may weaken the pharmacological action of the latter.

No clinically significant interactions with bisphosphonates have been reported.

Application features

Anastrozole Sandoz should not be used in premenopausal women.

Menopause should be confirmed by biochemical tests (luteinizing hormone (LH), follicle-stimulating hormone (FSH) and/or estradiol levels). There are no data on the use of anastrozole with luteinizing hormone-releasing factor (LHRH) analogues. The concomitant use of anastrozole and tamoxifen or estrogen-containing products should be avoided as this may reduce their pharmacological effects. The risks and benefits of anastrozole treatment in patients with pre-existing coronary artery disease should be considered (see section 4.8).

Liver dysfunction

There are no data on the safety of Anastrozole Sandoz in patients with moderate to severe hepatic impairment. Exposure to anastrozole may be increased in patients with hepatic impairment; caution should be exercised when using Anastrozole Sandoz in patients with moderate to severe hepatic impairment. Treatment should be based on an assessment of the benefit-risk ratio for each individual patient.

Kidney dysfunction

There are no data on the safety of using Anastrozole Sandoz in patients with severe renal impairment (glomerular filtration rate below 30 ml/min). The use of the drug in patients with severe renal impairment requires caution.

Effect on bone mineral density

Since Anastrozole reduces circulating oestrogen levels, this may lead to a decrease in bone mineral density with a possible increase in the risk of fracture. In women with osteoporosis or at risk of osteoporosis, bone mineral density should be assessed by bone densitometry, e.g. DEXA scan, at the start of treatment and regularly thereafter. If necessary, osteoporosis treatment or prevention should be initiated and the patient should be monitored. The use of specific agents, e.g. bisphosphonates, may halt further loss of bone mineral density caused by anastrozole in postmenopausal women and should be considered.

This medicine contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Use during pregnancy or breastfeeding

Animal studies have shown reproductive toxicity.

There are no data on the use of anastrozole in pregnant and lactating women.

Anastrozole Sandoz is contraindicated during pregnancy or breast-feeding. The effect on human fertility has not been studied.

Ability to influence reaction speed when driving vehicles or other mechanisms

Anastrozole Sandoz has no or negligible influence on the ability to drive and use machines. However, due to reports of asthenia and drowsiness associated with the use of the drug, caution is advised when driving or operating machinery.

Method of administration and doses

Anastrozole Sandoz is taken orally.

Adult women, including elderly women, take 1 tablet (1 mg) orally once a day.

For hormone receptor-positive, early invasive breast cancer in postmenopausal women, the recommended duration of adjuvant endocrine treatment is 5 years.

Renal impairment: No dose adjustment is required in patients with mild or moderate renal impairment. Anastrozole Sandoz should be used with caution in patients with severe renal impairment.

Hepatic impairment: No dose adjustment is required in patients with mild liver disease. Patients with moderate to severe hepatic impairment should use the drug with caution.

Children. Anastrozole SANDOZ is not recommended for use in children.

Overdose

Clinical experience with accidental overdose is limited. In animal studies, anastrozole has shown low acute toxicity. In clinical studies, various doses of anastrozole were used: up to 60 mg once in healthy male volunteers and up to 10 mg per day in postmenopausal women with advanced breast cancer; these doses were well tolerated. A single dose of anastrozole that results in life-threatening symptoms has not been established. There is no specific antidote; treatment is symptomatic.

In the treatment of overdose, the possibility of multiple ingestions should be considered. If the patient is not unconscious, vomiting may be induced. Dialysis may be useful, as anastrozole is not highly protein bound. General supportive care is recommended, including frequent monitoring of vital signs and close observation of the patient.

Adverse reactions

The table presents adverse reactions observed during clinical and post-marketing studies or received as spontaneous reports.

The following adverse reactions are listed by frequency and system organ class. The frequency of occurrence is defined using the following convention: very common (≥1/10), common (≥1/100, <1/10), uncommon (≥1/1,000, <1/100), rare (≥1/10,000, <1/1,000) and rare (<1/10,000). The most frequently reported adverse reactions are: headache, flushing, nausea, rash, arthralgia, joint mobility disorders, arthritis and asthenia.

*Vaginal bleeding has been commonly reported, occurring predominantly in patients with advanced breast cancer during the first few weeks after switching from hormonal therapy to anastrozole treatment. If bleeding persists, the patient should be further evaluated.

** Cases of carpal tunnel syndrome were observed significantly more frequently in patients treated with anastrozole during clinical trials than in those treated with tamoxifen.

In a study of postmenopausal women with operable breast cancer treated for 5 years, ischemic cardiovascular events were more common in patients treated with anastrozole compared with those treated with tamoxifen, although the difference was not statistically significant. The observed difference was mainly due to reports of angina pectoris and was associated with a subgroup of patients with pre-existing ischemic heart disease.

Anastrozole Sandoz reduces circulating estrogen levels, which may cause a decrease in bone mineral density, which may increase the risk of fractures in some patients.

Expiration date

3 years.

Storage conditions

Store at a temperature not exceeding 30 °C. Store in the original package in order to protect from light. Keep out of the reach of children.

Packaging

14 tablets in a blister; 2 blisters in a cardboard box.

Vacation category

According to the recipe.

Producer

Salutas Pharma GmbH.

Address

Otto-von-Güricke-Allee 1, 39179, Barleben, Germany.